title: 5-HT2A receptors in the feline brain: 123I-5-I-R91150 kinetics and the influence of ketamine measured with micro-SPECT.
abstract: Subanesthetic doses of ketamine can be used as a rapid-acting antidepressant in patients with treatment-resistant depression. Therefore, the brain kinetics of (123)I-5-I-R91150 (4-amino-N-[1-[3-(4-fluorophenyl)propyl]-4-methylpiperidin-4-yl]-5-iodo-2-methoxybenzamide) and the influence of ketamine on the postsynaptic serotonin-2A receptor (5-hydroxytryptamine-2A, or 5-HT2A) status were investigated in cats using micro-SPECT.
  
  
  METHODS
  This study was conducted on 6 cats using the radioligand (123)I-5-I-R91150, a 5-HT2A receptor antagonist, as the imaging probe. Anesthesia was induced and maintained with a continuous-rate infusion of propofol (8.4 ± 1.2 mg kg(-1) followed by 0.22 mg kg(-1) min(-1)) 75 min after tracer administration, and acquisition of the first image began 15 min after induction of anesthesia. After this first acquisition, propofol (0.22 mg kg(-1) min(-1)) was combined with ketamine (5 mg kg(-1) followed by 0.023 mg kg(-1) min(-1)), and the second acquisition began 15 min later. Semiquantification, with the cerebellum as a reference region, was performed to calculate the 5-HT2A receptor binding indices (parameter for available receptor density) in the frontal and temporal cortices. The binding indices were analyzed with Wilcoxon signed ranks statistics.
  
  
  RESULTS
  The addition of ketamine to the propofol continuous-rate infusion resulted in decreased binding indices in the right frontal cortex (1.25 ± 0.22 vs. 1.45 ± 0.16; P = 0.028), left frontal cortex (1.34 ± 0.15 vs. 1.49 ± 0.10; P = 0.028), right temporal cortex (1.30 ± 0.17 vs. 1.45 ± 0.09; P = 0.046), and left temporal cortex (1.41 ± 0.20 vs. 1.52 ± 0.20; P = 0.046).
  
  
  CONCLUSIONS
  This study showed that cats can be used as an animal model for studying alterations of the 5-HT2A receptor status with (123)I-5-I-R91150 micro-SPECT. Furthermore, an interaction between ketamine and the 5-HT2A receptors resulting in decreased binding of (123)I-5-I-R91150 in the frontal and temporal cortices was demonstrated. Whether the decreased radioligand binding resulted from a direct competition between ketamine and (123)I-5-I-R91150 or from a decreased affinity of the 5-HT2A receptor caused by ketamine remains to be elucidated.
authors.affiliation: Department of Medicine and Clinical Biology of Small Animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium. tim.waelbers@ugent.be
authors.forename: Tim
authors.initials: T
authors.lastname: Waelbers
authors.forename: Ingeborgh
authors.initials: I
authors.lastname: Polis
authors.forename: Simon
authors.initials: S
authors.lastname: Vermeire
authors.forename: André
authors.initials: A
authors.lastname: Dobbeleir
authors.forename: Jos
authors.initials: J
authors.lastname: Eersels
authors.forename: Bart
authors.initials: B
authors.lastname: De Spiegeleer
authors.forename: Kurt
authors.initials: K
authors.lastname: Audenaert
authors.forename: Guido
authors.initials: G
authors.lastname: Slegers
authors.forename: Kathelijne
authors.initials: K
authors.lastname: Peremans
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism*; D002415:Cats; D005260:Female; D007649:Ketamine / Q000494:pharmacology*; D007700:Kinetics; D010880:Piperidines / Q000378:metabolism*; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: C504893:5-iodo-R 91150; D010880:Piperidines; D044402:Receptor, Serotonin, 5-HT2A; D007649:Ketamine
keywords: 5-HT2A; SPECT; brain; cats; ketamine